EP1423419B1 - Hybrid and tandem expression of neisserial proteins - Google Patents

Hybrid and tandem expression of neisserial proteins Download PDF

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Publication number
EP1423419B1
EP1423419B1 EP02777592A EP02777592A EP1423419B1 EP 1423419 B1 EP1423419 B1 EP 1423419B1 EP 02777592 A EP02777592 A EP 02777592A EP 02777592 A EP02777592 A EP 02777592A EP 1423419 B1 EP1423419 B1 EP 1423419B1
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EP
European Patent Office
Prior art keywords
protein
antigen
amino acid
acid sequence
neisserial
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EP02777592A
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German (de)
English (en)
French (fr)
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EP1423419A2 (en
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Mariagrazia Chiron S.P.A. Pizza
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GSK Vaccines SRL
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Novartis Vaccines and Diagnostics SRL
Novartis Vaccines and Diagnostics Inc
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Priority to EP10179788.4A priority Critical patent/EP2360176B1/en
Priority to DK10179788.4T priority patent/DK2360176T3/en
Priority to EP14172613.3A priority patent/EP2829549A3/en
Priority to DK10179755.3T priority patent/DK2327719T3/da
Priority to EP10179755.3A priority patent/EP2327719B1/en
Application filed by Novartis Vaccines and Diagnostics SRL, Novartis Vaccines and Diagnostics Inc filed Critical Novartis Vaccines and Diagnostics SRL
Publication of EP1423419A2 publication Critical patent/EP1423419A2/en
Publication of EP1423419B1 publication Critical patent/EP1423419B1/en
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Priority to CY20111100383T priority patent/CY1113218T1/el
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/095—Neisseria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/22—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Neisseriaceae (F)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/53—DNA (RNA) vaccination
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505—Inorganic adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • This invention is in the field of protein expression.
  • it relates to the expression of proteins from Neisseria (e.g. N.gonorrhoeae or, preferably, N.meningitidis ).
  • References 1 and 2 disclose alternative and improved approaches for the expression of the Neisserial proteins disclosed in references 3 to 6.
  • One such method is to produce 'hybrid' proteins in which two or more Neisserial proteins are expressed as a single polypeptide chain.
  • This approach offers two advantages. First, a protein that may be unstable or poorly expressed on its own can be assisted by adding a suitable hybrid partner that overcomes the problem. Second, commercial manufacture is simplified as only one expression and purification need be employed in order to produce two separately-useful proteins.
  • the invention provides a method for the simultaneous expression of two Neisserial proteins, in which said two or more proteins are joined such that they are translated as a single polypeptide chain.
  • the hybrid proteins of the invention can be represented by the formula: NH 2 -A-[-X-L-] n -B-COOH wherein X is an amino acid sequence, L is an optional linker amino acid sequence, A is an optional N-terminal amino acid sequence, B is an optional C-terminal amino acid sequence, and n is 2.
  • the 2 -X-moieties are 741, and ; or
  • a -X-moiety has a leader peptide sequence in its wild-type form, this may be included or omitted in described the hybrid proteins in full-length form, it is preferably at the C-terminal end of a hybrid protein; if it is to be used at the N-terminus, if is preferred to use a AG form of 741.
  • linker amino acid sequence -L- may be present or absent.
  • the hybrid may be NH 2 -X 1 -L 1 -X 2 -L 2 -COOH, NH 2 -X 1 -X 2 -COOH, NH 2 -X 1 -L 1 -X 2 COOH, NH 2 -X 1 -X 2 -L 2 -COOH, etc.
  • a useful linker is GSGGGG (SEQ ID 27), with the Gly-Ser dipeptide being formed from a Bam HI restriction site, thus aiding cloning and manipulation, and the Gly 4 tetrapeptide being a typical poly-glycine linker.
  • X n+1 is a ⁇ G protein and L n is a glycine linker, this may be equivalent to X n+1 , not being a ⁇ G protein and L n being absent.
  • -B- is an optional C-terminal amino acid sequence.
  • This will typically be short (e.g. 40 or fewer amino acids i.e . 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1).
  • Other suitable C-terminal amino acid sequences will be apparent to those skilled in the art.
  • the invention can use amino acid sequences from any strains of N.meningitidis. References to a particular protein therefore include that protein from any strain. Sequence variations between strains are included within (b)
  • Reference sequences from N.meningitidis serogroup B include:
  • sequence listing herein includes polymorphic forms of proteins 741 (SEQ IDs 1-22) and which have been identified:
  • Preferred proteins of the invention comprise -X- moieties having an amino acid sequence found in N.meningitidis serogroup B.
  • individual -X- moieties may be from one or more strains.
  • X 2 may be from the same strain as X 1 or from a different strain.
  • preferred -X- moieties are from strains 2996, MC58, 95N477, or 394/98.
  • Strain 95N477 is sometimes referred to herein as 'ET-37', this being its electrophoretic type.
  • Strain 394/98 is sometimes referred to herein as 'nz', as it is a New Zealand strain.
  • 741 is preferably from serogroup B strains MC58, 2996, 394/98, or 95N477, or from serogroup C strain 90/18311.
  • Strains are indicated as a subscript e.g. 741 MC58 is protein 741 from strain MC58. Unless otherwise stated, proteins mentioned herein (e.g. with no subscript) are from N.meningitidis strain 2996, which can be taken as a 'reference' strain. It will be appreciated, however, that the invention is not in general limited by strain. As mentioned above, general references to a protein may be taken to include that protein from any strain. This will typically have sequence identity to 2996 of 90% or more (eg. 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more).
  • the invention also provides a protein having an amino acid sequence from SEQ IDs 1 to 22. It also provides proteins and nucleic acid having sequence identity to these. As described above, the degree of 'sequence identity' is greater than 90%,
  • the invention provides nucleic acid encoding such proteins.
  • the invention also provides nucleic acid encoding proteins according to the invention.
  • nucleic acid comprising sequences complementary to those described above (eg . for antisense or probing purposes).
  • Nucleic acid according to the invention can, of course, be prepared in many ways ( eg . by chemical synthesis, from genomic or cDNA libraries, from the organism itself etc.) and can take various forms (eg. single stranded, double stranded, vectors, probes etc.).
  • nucleic acid includes DNA and RNA, and also their analogues, such as those containing modified backbones, and also peptide nucleic acids (PNA) etc.
  • the invention also provides a composition comprising two or more ( i.e . 2, 3, 4, 5. 6 or 7) of the following proteins:
  • the mixture may include one or both of the following proteins, either in combination with two or more of (I) to (7), or in combination with only one of (1) to (7):
  • a preferred mixture comprises the following three proteins:
  • the present invention preferably utilises a heterologous host.
  • the heterologous host may be prokaryotic (e.g . a bacterium) or eukaryotic. It is preferably E.coli, but other suitable hosts include Bacillus subtilis, Vibrio cholerae, Salmonella typhi, Salmonenna typhimurium, Neisseria lactamica, Neisseria cinerea, Mycobacteria ( e.g. M.tuberculosis ), yeast etc.
  • the invention provides (a) nucleic acid encoding the proteins described above (b) vectors comprising these nucleic acid sequences (c) host cells containing said vectors (d) compositions comprising the proteins or nucleic acids of the invention, which may be suitable as immunogenic compositions (e.g . vaccines) or as diagnostic reagents (e) these compositions for use as medicaments ( e.g .
  • compositions for treating or preventing infection due to Neisserial bacteria
  • diagnostic reagent for detecting the presence of Neisserial bacteria or of antibodies raised against Neisseria bacteria
  • a reagent which can raise antibodies against Neisseria bacteria for detecting the presence of Neisserial bacteria or of antibodies raised against Neisseria bacteria
  • a method of treating a patient comprising administering to the patient a therapeutically effective amount of these compositions.
  • Implementing the invention will typically involve the basic steps of: obtaining a first nucleic acid encoding a first protein; obtaining a second nucleic acid encoding a second protein; and ligating the first and second nucleic acids.
  • the resulting nucleic acid may be inserted into an expression vector, or may already be part of an expression vector.
  • purification of hybrid proteins may involve the refolding techniques disclosed herein.
  • compositions of the invention are preferably immunogenic composition, and are more preferably vaccine compositions.
  • the pH of the composition is preferably between 6 and 7.
  • the pH may be maintained by the use of a buffer.
  • the composition may be sterile.
  • Vaccines according to the invention may either be prophylactic (i.e . to prevent infection) or therapeutic (i.e . to treat infection), but will typically be prophylactic.
  • the invention also provides a composition of the invention for use as a medicament.
  • the medicament is preferably able to raise an immune response in a mammal ( i.e . it is an immunogenic composition) and is more preferably a vaccine.
  • the invention also provides the use of a composition of the invention in the manufacture of a medicament for raising an immune response in a mammal.
  • the medicament is preferably a vaccine.
  • the invention also provides a method for raising an immune response in a mammal comprising the step of administering an effective amount of a composition of the invention.
  • the immune response is preferably protective.
  • the method may raise a booster response.
  • the mammal is preferably a human.
  • the human is preferably a child (e.g. a toddler or infant); where the vaccine is for prophylactic use, the human is preferably an adult.
  • a vaccine intended for children may also be administered to adults e.g . to assess safety, dosage, immunogenicity, etc.
  • These uses and methods are preferably for the prevention and/or treatment of a disease caused by a Neisseria (e.g. meningitis, septicaemia, gonorrhoea etc.).
  • a Neisseria e.g. meningitis, septicaemia, gonorrhoea etc.
  • the prevention and/or treatment of bacterial meningitis is preferred.
  • composition of the invention will typically, in addition to the components mentioned above, comprise one or more pharmaceutically acceptable carriers', which include any carrier that does not itself induce the production of antibodies harmful to the individual receiving the composition.
  • Suitable carriers are typically large, slowly metabolised macromolecules such as proteins, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers, trehalose ( WO00/56365 ) and lipid aggregates (such as oil droplets or liposomes).
  • Suitable carriers are typically large, slowly metabolised macromolecules such as proteins, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers, trehalose ( WO00/56365 ) and lipid aggregates (such as oil droplets or liposomes).
  • trehalose WO00/56365
  • lipid aggregates such as oil droplets or liposomes.
  • Such carriers are well known to those of ordinary skill in the art.
  • the vaccines
  • Immunogenic compositions used as vaccines comprise an immunologically effective amount of antigen, as well as any other of the above-mentioned components, as needed.
  • 'immunologically effective amount' it is meant that the administration of that amount to an individual, either in a single dose or as part of a series, is effective for treatment or prevention. This amount varies depending upon the health and physical condition of the individual to be treated, age, the taxonomic group of individual to be treated ( e.g . non-human primate, primate, etc.), the capacity of the individual's immune system to synthesise antibodies, the degree of protection desired, the formulation of the vaccine, the treating doctor's assessment of the medical situation, and other relevant factors.
  • Dosage treatment may be a single dose schedule or a multiple dose schedule ( e.g . including booster doses).
  • the vaccine may be administered in conjunction with other immunoregulatory agents.
  • the vaccine may be administered in conjunction with other immunoregulatory agents.
  • the composition may include other adjuvants in addition to (or in place of) the aluminium salt.
  • Preferred adjuvants to enhance effectiveness of the composition include, but are not limited to: (1) oil-in-water emulsion formulations (with or without other specific immunostimulating agents such as muramyl peptides (see below) or bacterial cell wall components), such as for example (a) MF59TM ( WO90/14837 Chapter 10 in ref.
  • RibiTM adjuvant system Ribi Immunochem, Hamilton, MT
  • MPL monophosphorylipid A
  • TDM trehalose dimycolate
  • CWS cell wall skeleton
  • saponin adjuvants such as QS21 or Stimulon TM
  • cytokines such as interleukins (e.g. IL-1. IL-2, IL-4, IL-5, IL-6, IL-7, IL-12 ( WO99/44636 ), etc .), interferons (e.g . gamma interferon), macrophage colony stimulating factor (M-CSF), tumor necrosis factor (TNF), etc .; (5) monophosphoryl lipid A (MPL) or 3-0-deacytated MPL (3dMPL) e.g .
  • MPL monophosphoryl lipid A
  • 3dMPL monophosphoryl lipid A
  • GB-2220221 EP-A-0689454 ; (6) combinations of 3dMPL with, for example, QS21 and/or oil-in-water emulsions e.g. EP-A-0835318 , EP-A-0735898 , EP-A-0761231 ; (7) oligonucleotides comprising CpG motifs [ Krieg Vaccine 2000, 19, 618-622 ; Krieg Curr- opin Mol Ther 2001 3:15-24 ; Roman et al., Nat. Med., 1997, 3, 849-854 ; Weiner et al., PNAS USA, 1997, 94, 10833-10837 ; Davis et al., J.
  • WO99/52549 (9) a polyoxyethylene sorbitan ester surfactant in combination with an octoxynol ( e.g . WO01/21207 ) or a polyoxyethylene alkyl ether or ester surfactant in combination with at least one additional nonionic surfactant such as an octoxynol ( e . g . WO01/21152 ); (10) an immunostimulatory oligonucleotide (e . g . a CpG oligonucleotide) and a saponin e.g . WO00/62800 ; (11) an immunostimulant and a particle of metal salt e . g .
  • WO00/23105 (12) a saponin and an oil-in-water emulsion e.g ., WO99/11241 ; (13) a saponin ( e.g. QS21) + 3dMPL + lL-12 (optionally + a sterol) e . g . WO98/57659 ; (14) other substances that act as immunostimulating agents to enhance the efficacy of the composition.
  • Muramyl peptides include N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr-MDP), N-acetyl-nonnuramyl-L-alanyl-D-isoglutamine (nor-MDP), N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-(1'-2'-dipalmitoyl- sn -glycero-3-hydroxyphosphoryloxy)-ethylamine MTP-PE), etc.
  • thr-MDP N-acetyl-muramyl-L-threonyl-D-isoglutamine
  • nor-MDP N-acetyl-nonnuramyl-L-alanyl-D-isoglutamine
  • N-MDP N-acetylmuramyl-L-alanyl-D-isoglutaminy
  • composition of the invention include:
  • composition may comprise one or more of these further antigens.
  • a saccharide or carbohydrate antigen is used, it is preferably conjugated to a carrier protein in order to enhance immunogenicity [ e.g . refs. 54 to 63].
  • Preferred carrier proteins are bacterial toxins or toxoids, such as diphtheria or tetanus toxoids.
  • the CRM 197 diphtheria toxoid is particularly preferred.
  • Other suitable carrier proteins include the N.meningitidis outer membrane protein [ e.g . ref. 64], synthetic peptides [ e . g . 65, 66], heat shock proteins [ e . g . 67], pertussis proteins [ e . g .
  • a mixture comprises capsular saccharides from both serogroups A and C
  • the ratio (w/w) of MenA saccharide:MenC saccharide is greater than 1 (e.g. 2:1, 3:1, 4:1, 5:1, 10: or higher). Saccharides from different serogroups of N.meningitidis may be conjugated to the same or different carrier proteins.
  • Toxic protein antigens may be detoxified where necessary (e . g . detoxification of pertussis toxin by chemical and/or genetic means [32]).
  • diphtheria antigen is included in the composition it is preferred also to include tetanus antigen and pertussis antigens. Similarly, where a tetanus antigen is included it is preferred also to include diphtheria and pertussis antigens. Similarly, where a pertussis antigen is included it is preferred also to include diphtheria and tetanus antigens.
  • Antigens are preferably mixed with (and more preferably adsorbed to) an aluminium salt (e.g. phosphate, hydroxide, hydroxyphosphate, oxyhydroxide, orthophosphate, sulphate).
  • the salt may take any suitable form (e.g. gel, crystalline, amorphous etc.).
  • Antigens in the composition will typically be present at a concentration of at least 1 ⁇ g/ml each. In general, the concentration of any given antigen will be sufficient to elicit an immune response against that antigen.
  • nucleic acid encoding the antigen may be used [ e.g . refs. 72 to 80]. Protein components of the compositions of the invention may thus be replaced by nucleic acid (preferably DNA e.g. in the form of a plasmid) that encodes the protein.
  • composition comprising X may consist exclusively of X or may include something additional e.g. X + Y.
  • Hybrid proteins - X 1 961c or 961cL
  • Titres obtained after immunisation with 961c-741 [refs. 1 & 2] were as follows: Strain (scrogroup) 2996 (B) MC58 (B) 394/98 (B) 44176 (B) F6124 (A) BZ133 (C) Al hydroxide 65536 32768 4096 >32768 16384 >2048 FCA >16384 262144 4096 >16384 - >2048
  • Results obtained after immunisation with proteins disclosed in refs. 1 & 2 were as follows: n X 1 L 1 X 2 L 2 Bactericidal titre ELISA FCA Alum FCA Alum 2 ORF46.1 - 961 (His) 6 8192 8192 21558 >109350 - 961 c (His) 6 8192 128 9020 76545
  • Titres using protein #4 were as follows: Strain (serogroup) 2996 (B) MC58 (B) 394198 (B) 44/76 (B) F6124 (A) Al hydroxide 256 >262144 >2048 32768 8192 FCA 1024 >262144 >2048 >32768 >32768
  • Titres using protein #7 were as follows: Strain (serogroup) 2996 (B) MC58 (B) 394/98 (B) 44/76 (B) F6124 (A) BZ133 (c) Al hydroxide 256 130000 16000 32000 8000 16000
  • mice were immunised with of three proteins adjuvanted with aluminium hydroxide, either single or in a triple combination: (1) 287 Nz -953; (2) 936-741; and (3) 961c.
  • the mixture was able to induce high bactericidal titres against various strains: 2996 (B) MC58 (B) NGH38 394/98 (B) H44/76 (B) F6124 (A) BZ133 (C) C11 (C) (1) 32000 16000 130000 16000 32000 8000 16000 8000 (2) 256 131000 128 16000 32000 8000 16000 ⁇ 4 (3) 32000 8000 - - 8000 - 32000 mix 32000 32000 65000 16000 260000 65000 >65000 8000 (X) 4000 4000 1000 1000 >4000 1000 4000 n.d. '-' indicates that this strain contains no NadA gene (X) was a combination of protein 287 with outer membrane vesicles, for comparison

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EP02777592A 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial proteins Expired - Lifetime EP1423419B1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
DK10179788.4T DK2360176T3 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserialt derived proteins
EP14172613.3A EP2829549A3 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial derived proteins
DK10179755.3T DK2327719T3 (da) 2001-09-06 2002-09-06 Hybrid- og tandemekspression af neisseria-proteiner
EP10179755.3A EP2327719B1 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial proteins
EP10179788.4A EP2360176B1 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial derived proteins
CY20111100383T CY1113218T1 (el) 2001-09-06 2011-04-15 Υβριδιο και διμερης εκφραση πρωτεϊνων ναϊσσεριας

Applications Claiming Priority (3)

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GB0121591 2001-09-06
GBGB0121591.2A GB0121591D0 (en) 2001-09-06 2001-09-06 Hybrid and tandem expression of neisserial proteins
PCT/IB2002/003904 WO2003020756A2 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial proteins

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Application Number Title Priority Date Filing Date
EP10179755.3A Division EP2327719B1 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial proteins
EP14172613.3A Division EP2829549A3 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial derived proteins
EP10179788.4A Division EP2360176B1 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial derived proteins
EP10179755.3 Division-Into 2010-09-25
EP10179788.4 Division-Into 2010-09-26

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EP1423419A2 EP1423419A2 (en) 2004-06-02
EP1423419B1 true EP1423419B1 (en) 2011-01-19

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EP02777592A Expired - Lifetime EP1423419B1 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial proteins
EP10179788.4A Expired - Lifetime EP2360176B1 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial derived proteins
EP10179755.3A Revoked EP2327719B1 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial proteins
EP14172613.3A Withdrawn EP2829549A3 (en) 2001-09-06 2002-09-06 Hybrid and tandem expression of neisserial derived proteins

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Families Citing this family (83)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG152917A1 (en) * 1998-01-14 2009-06-29 Chiron Srl Neisseria meningitidis antigens
EP2261350A3 (en) * 1998-05-01 2012-01-04 Novartis Vaccines and Diagnostics, Inc. Neisseria meningitidis antigens and compositions
US20070026021A1 (en) * 1998-05-01 2007-02-01 Chiron S.R.I. Neisseria meningitidis antigens and compositions
US7368261B1 (en) 1999-04-30 2008-05-06 Novartis Vaccines And Diagnostics Srl Conserved Neisserial antigens
GB9911683D0 (en) * 1999-05-19 1999-07-21 Chiron Spa Antigenic peptides
EP2258851A1 (en) * 1999-05-19 2010-12-08 Novartis Vaccines and Diagnostics S.r.l. Combination neisserial compositions
EP1801219B1 (en) * 1999-10-29 2015-10-14 GlaxoSmithKline Biologicals S.A. Neisserial antigenic peptides
GB9928196D0 (en) 1999-11-29 2000-01-26 Chiron Spa Combinations of B, C and other antigens
ATE476988T1 (de) * 2000-01-17 2010-08-15 Novartis Vaccines & Diagnostic Membranvesikel (omv) impfstoff, der n. meningitidis serogruppe b membranproteine enthält
PT1790660E (pt) 2000-02-28 2012-09-17 Novartis Vaccines & Diagnostic Expressão heteróloga de proteínas de neisseria
GB0115176D0 (en) 2001-06-20 2001-08-15 Chiron Spa Capular polysaccharide solubilisation and combination vaccines
GB0118249D0 (en) 2001-07-26 2001-09-19 Chiron Spa Histidine vaccines
BR0211494A (pt) * 2001-07-27 2004-08-17 Chiron Srl Adesinas de meningococo nada, app e orf 40
GB0121591D0 (en) 2001-09-06 2001-10-24 Chiron Spa Hybrid and tandem expression of neisserial proteins
AR045702A1 (es) 2001-10-03 2005-11-09 Chiron Corp Composiciones de adyuvantes.
US7838015B2 (en) 2001-10-03 2010-11-23 Novartis Vaccines And Diagnostics, Inc. Adjuvanted meningococcus compositions
MX339524B (es) 2001-10-11 2016-05-30 Wyeth Corp Composiciones inmunogenicas novedosas para la prevencion y tratamiento de enfermedad meningococica.
NZ587398A (en) * 2002-08-02 2012-03-30 Glaxosmithkline Biolog Sa Neisserial bleb preparations and vaccines comprising them
GB0220194D0 (en) 2002-08-30 2002-10-09 Chiron Spa Improved vesicles
US7785608B2 (en) 2002-08-30 2010-08-31 Wyeth Holdings Corporation Immunogenic compositions for the prevention and treatment of meningococcal disease
HUE031886T2 (en) * 2002-10-11 2017-08-28 Glaxosmithkline Biologicals Sa Polypeptide vaccines for extensive protection against hypervirulent meningococcal lines
DE60332477D1 (de) 2002-11-15 2010-06-17 Novartis Vaccines & Diagnostic Unerwartete oberflächenproteine in neisseria meningitidis
GB0227346D0 (en) * 2002-11-22 2002-12-31 Chiron Spa 741
PT2191844E (pt) 2003-01-30 2014-06-04 Novartis Ag Vacinas injetáveis contra múltiplos serogrupos meningocócicos
RU2378010C2 (ru) * 2003-10-02 2010-01-10 Новартис Вэксинес Энд Дайэгностикс С.Р.Л. Жидкие вакцины для множественных серогрупп менингококков
GB0323103D0 (en) 2003-10-02 2003-11-05 Chiron Srl De-acetylated saccharides
GB0408977D0 (en) 2004-04-22 2004-05-26 Chiron Srl Immunising against meningococcal serogroup Y using proteins
GB0415160D0 (en) * 2004-07-06 2004-08-11 Chiron Srl Inhibitors of bacterial infection
GB0419408D0 (en) * 2004-09-01 2004-10-06 Chiron Srl 741 chimeric polypeptides
JP2008530245A (ja) 2005-02-18 2008-08-07 ノバルティス ヴァクシンズ アンド ダイアグノスティクス， インコーポレイテッド 尿路病原性菌株由来の抗原
DK1858920T3 (en) 2005-02-18 2016-02-29 Glaxosmithkline Biolog Sa PROTEINS AND NUCLEIC ACIDS FROM MENINGITIS / SEPSIS-ASSOCIATED ESCHERICHIA COLI
AU2013201318B2 (en) * 2005-11-25 2015-11-19 Glaxosmithkline Biologicals Sa Chimeric, hybrid and tandem polypeptides of meningococcal NMB 1870
GB0524066D0 (en) 2005-11-25 2006-01-04 Chiron Srl 741 ii
US20110008279A1 (en) * 2005-12-06 2011-01-13 Vega Masignani Methods and Compositions Relating to Adhesins as Adjuvants
EP2586790A3 (en) 2006-08-16 2013-08-14 Novartis AG Immunogens from uropathogenic Escherichia coli
AR064642A1 (es) 2006-12-22 2009-04-15 Wyeth Corp Polinucleotido vector que lo comprende celula recombinante que comprende el vector polipeptido , anticuerpo , composicion que comprende el polinucleotido , vector , celula recombinante polipeptido o anticuerpo , uso de la composicion y metodo para preparar la composicion misma y preparar una composi
GB0700562D0 (en) 2007-01-11 2007-02-21 Novartis Vaccines & Diagnostic Modified Saccharides
GB0713880D0 (en) 2007-07-17 2007-08-29 Novartis Ag Conjugate purification
SI2200642T1 (sl) 2007-10-19 2012-06-29 Novartis Ag Formulacije meningokoknega cepiva
NZ587382A (en) 2008-02-21 2012-01-12 Novartis Ag Meningococcal fhbp polypeptides
SI2268618T1 (sl) 2008-03-03 2015-09-30 Novartis Ag Spojine in sestavki kot modulatorji aktivnosti TLR
US9511131B2 (en) * 2008-03-10 2016-12-06 Children's Hospital & Research Center Oakland Chimeric factor H binding proteins (fHBP) containing a heterologous B domain and methods of use
US20100105875A1 (en) * 2008-06-09 2010-04-29 Maria Scarselli Antibodies against neisserial factor H binding protein
CN102300585A (zh) * 2008-12-17 2011-12-28 诺华有限公司 包含血红蛋白受体的脑膜炎球菌疫苗
ES2797504T3 (es) 2009-03-24 2020-12-02 Glaxosmithkline Biologicals Sa Proteína de enlace del factor H meningocócico utilizada como adyuvante
JP5883380B2 (ja) * 2009-04-30 2016-03-15 チルドレンズ ホスピタル アンド リサーチ センター アット オークランド キメラ因子ｈ結合タンパク質（ｆｈｂｐ）およびその使用方法
CN102762226A (zh) 2009-06-10 2012-10-31 诺华有限公司 含苯并萘啶的疫苗
WO2011008400A2 (en) 2009-06-16 2011-01-20 Novartis Ag High-throughput complement-mediated antibody-dependent and opsonic bactericidal assays
AU2010288240B2 (en) 2009-08-27 2014-03-27 Novartis Ag Hybrid polypeptides including meningococcal fHBP sequences
TWI445708B (zh) 2009-09-02 2014-07-21 Irm Llc 作為ｔｌｒ活性調節劑之化合物及組合物
MX2012002723A (es) 2009-09-02 2012-04-11 Novartis Ag Composiciones inmunogenicas que incluyen moduladores de la actividad de receptores tipo toll.
EP2483390A2 (en) 2009-09-30 2012-08-08 Novartis AG Expression of meningococcal fhbp polypeptides
CA2779816A1 (en) 2009-10-27 2011-05-05 Novartis Ag Modified meningococcal fhbp polypeptides
WO2011057148A1 (en) 2009-11-05 2011-05-12 Irm Llc Compounds and compositions as tlr-7 activity modulators
BR112012014624A8 (pt) 2009-12-15 2017-12-26 Novartis Ag suspensão homogênea de compostos de imunopotenciação e usos dos destes
JP5363381B2 (ja) * 2010-03-09 2013-12-11 パナソニック株式会社 プラズマディスプレイパネル
US8808703B2 (en) 2010-03-23 2014-08-19 Tom Yao-Hsiang Wu Compounds (cystein based lipopeptides) and compositions as TLR2 agonists used for treating infections, inflammations, respiratory diseases etc
BR122022015250B1 (pt) 2010-03-30 2023-11-07 Children´S Hospital & Research Center At Oakland Composições imunogênicas e seus usos
WO2011161653A1 (en) 2010-06-25 2011-12-29 Novartis Ag Combinations of meningococcal factor h binding proteins
SI2608805T2 (sl) 2010-08-23 2025-09-30 Wyeth Llc Stabilne formulacije antigenov rLP2086 neisserie meningitidis
BR112013005329A2 (pt) 2010-09-10 2017-05-02 Wyeth Llc variantes não lipidadas de antígenos orf2086 de neisseria meningitidis
BR112013005626B1 (pt) 2010-09-10 2022-07-26 Glaxosmithkline Biologicals Sa Meningococo, processo para a preparação de uma cepa meningocócica, vesículas de membrana externa, composição farmacêutica imunogênica, e, uso de uma composição
CN102028941B (zh) * 2011-02-11 2013-02-13 中国医学科学院医学生物学研究所 一种b群脑膜炎球菌重组蛋白嵌合疫苗及其制备方法
US20140186861A1 (en) * 2011-07-11 2014-07-03 Uvic Industry Partnerships Inc. Soluble treponema pallidum protein tp0453, tp0453-tp0326 fusion protein, and use in syphilis diagnosis
CA2862247A1 (en) 2011-12-29 2013-07-04 Novartis Ag Adjuvanted combinations of meningococcal factor h binding proteins
SA115360586B1 (ar) 2012-03-09 2017-04-12 فايزر انك تركيبات لعلاج الالتهاب السحائي البكتيري وطرق لتحضيرها
MX2018011291A (es) 2012-03-09 2023-01-31 Pfizer Composiciones de neisseria meningitidis y metodos de las mismas.
NZ630133A (en) 2012-06-14 2016-10-28 Novartis Ag Vaccines for serogroup x meningococcus
CA2875391A1 (en) 2012-07-27 2014-01-30 Institut National De La Sante Et De La Recherche Medicale Cd147 as receptor for pilus-mediated adhesion of meningococci to vascular endothelia
WO2014136064A2 (en) 2013-03-08 2014-09-12 Pfizer Inc. Immunogenic fusion polypeptides
EP3027206A4 (en) * 2013-08-02 2017-03-08 Children's Hospital & Research Center Oakland Non-naturally occurring factor h binding proteins (fhbp) and methods of use thereof
BR112016004463A2 (pt) 2013-09-08 2017-10-17 Pfizer composições de neisseria meningitidis e métodos das mesmas
JP6786394B2 (ja) 2014-02-28 2020-11-18 グラクソスミスクライン バイオロジカルズ ソシエテ アノニム 改変髄膜炎菌ｆＨｂｐポリペプチド
CN112851768A (zh) 2014-07-23 2021-05-28 奥克兰儿童医院及研究中心 因子h结合蛋白变体及其使用方法
WO2016132294A1 (en) 2015-02-19 2016-08-25 Pfizer Inc. Neisseria meningitidis compositions and methods thereof
EP3506933A2 (en) * 2016-09-02 2019-07-10 GlaxoSmithKline Biologicals SA Vaccines for neisseria gonorrhoeae
AU2018215585B2 (en) 2017-01-31 2022-03-17 Pfizer Inc. Neisseria meningitidis compositions and methods thereof
MX2022003682A (es) 2019-09-27 2022-04-25 Pfizer Composiciones de neisseria meningitidis y metodos de las mismas.
US12053516B2 (en) 2021-02-19 2024-08-06 Sanofi Pasteur Inc. Meningococcal B recombinant vaccine
GB202115151D0 (en) 2021-10-21 2021-12-08 Glaxosmithkline Biologicals Sa Methods
GB202208089D0 (en) 2022-06-01 2022-07-13 Glaxosmithkline Biologicals Sa Immunogenic composition
GB202208093D0 (en) 2022-06-01 2022-07-13 Glaxosmithkline Biologicals Sa Immunogenic composition
TW202423477A (zh) 2022-08-03 2024-06-16 美商賽諾菲巴斯德公司 針對腦膜炎奈瑟氏菌b的含佐劑免疫原性組成物

Family Cites Families (109)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3679343D1 (de) 1985-03-28 1991-06-27 Chiron Corp Expression durch verwendung von fusionsgenen fuer proteinproduktion.
DE3622221A1 (de) 1986-07-02 1988-01-14 Max Planck Gesellschaft Verfahren zur gentechnologischen gewinnung von proteinen unter verwendung gramnegativer wirtszellen
EP0273116A3 (en) 1986-10-09 1990-05-02 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Gonococcal and meningococcal polypeptides, vaccines and diagnostics
GB8815795D0 (en) 1988-07-02 1988-08-10 Bkl Extrusions Ltd Glazing bead
DE3841091A1 (de) 1988-12-07 1990-06-13 Behringwerke Ag Synthetische antigene, verfahren zu ihrer herstellung und ihre verwendung
WO1990006696A2 (en) 1988-12-19 1990-06-28 Praxis Biologics, Inc. Meningococcal class 1 outer-membrane protein vaccine
NL8803111A (nl) 1988-12-19 1990-07-16 Nederlanden Staat Multivalent meningococcen klasse i buitenmembraaneiwit vaccin.
ES2055785T3 (es) 1989-01-17 1994-09-01 Eniricerche Spa Peptidos sinteticos y su uso como vehiculos universales para la preparacion de conjugados inmunogenos aptos para el desarrollo de vacunas sinteticas.
HU212924B (en) 1989-05-25 1996-12-30 Chiron Corp Adjuvant formulation comprising a submicron oil droplet emulsion
IT1237764B (it) 1989-11-10 1993-06-17 Eniricerche Spa Peptidi sintetici utili come carriers universali per la preparazione di coniugati immunogenici e loro impiego per lo sviluppo di vaccini sintetici.
ATE121947T1 (de) * 1989-12-14 1995-05-15 Ca Nat Research Council Verbessertes meningokokkale polysaccharidkonjugatvakzin.
CU22302A1 (es) * 1990-09-07 1995-01-31 Cigb Secuencia nucleotidica codificante para una proteina de la membrana externa de neisseria meningitidis y uso de dicha proteina en preparados vacunales
IE912559A1 (en) 1990-07-19 1992-01-29 Merck & Co Inc The class ii protein of the outer membrane of neisseria¹meningitidis, and vaccines containing same
IL98715A0 (en) 1990-08-13 1992-07-15 American Cyanamid Co Filamentous hemaglutinin of bodetella pertussis as a carrier molecule for conjugate vaccines
US5153312A (en) 1990-09-28 1992-10-06 American Cyanamid Company Oligosaccharide conjugate vaccines
DE69227898T2 (de) 1991-03-14 1999-05-12 Imclone Systems, Inc., New York, N.Y. Rekombinante hybride porinepitope
WO1993018150A1 (en) 1992-03-02 1993-09-16 Biocine S.P.A. Helicobacter pylori proteins useful for vaccines and diagnostics
IT1262896B (it) 1992-03-06 1996-07-22 Composti coniugati formati da proteine heat shock (hsp) e oligo-poli- saccaridi, loro uso per la produzione di vaccini.
FR2692592B1 (fr) 1992-06-19 1995-03-31 Pasteur Merieux Serums Vacc Fragments d'ADN codant pour les sous-unités du récepteur de la transferrine de Neisseria meningitidis et procédés les exprimant.
UA40597C2 (uk) 1992-06-25 2001-08-15 Смітклайн Бічем Байолоджікалс С.А. Вакцинна композиція,спосіб лікування ссавців, що страждають або сприйнятливі до інфекції, спосіб лікування ссавців, що страждають на рак, спосіб одержання вакцинної композиції, композиція ад'ювантів
RU2074728C1 (ru) * 1993-01-03 1997-03-10 Научно-исследовательский институт вакцин и сывороток им.И.И.Мечникова РАМН Липополисахарид из neisseria meningitidis, обладающий протективными и иммуногенными свойствами
EP1175912A1 (en) 1993-03-23 2002-01-30 SmithKline Beecham Biologics SA Vaccine compositions containing 3-O deacylated monophosphoryl lipid A
US5439808A (en) 1993-07-23 1995-08-08 North American Vaccine, Inc. Method for the high level expression, purification and refolding of the outer membrane group B porin proteins from Neisseria meningitidis
GB9326253D0 (en) 1993-12-23 1994-02-23 Smithkline Beecham Biolog Vaccines
US6165747A (en) 1993-12-30 2000-12-26 President & Fellows Of Harvard College Nucleic acids encoding hedgehog proteins
FR2720408B1 (fr) 1994-05-31 1996-08-14 Pasteur Merieux Serums Vacc Fragments Tbp2 de Neisseria meningitidis.
DE69535036T3 (de) 1994-07-15 2011-07-07 The University of Iowa Research Foundation, IA Immunomodulatorische oligonukleotide
US6207646B1 (en) 1994-07-15 2001-03-27 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
IL117483A (en) * 1995-03-17 2008-03-20 Bernard Brodeur MENINGITIDIS NEISSERIA shell protein is resistant to proteinase K.
GB9513261D0 (en) 1995-06-29 1995-09-06 Smithkline Beecham Biolog Vaccines
FR2739624B1 (fr) 1995-10-10 1997-12-05 Pasteur Merieux Serums Vacc Nouvelle sous-unite tbp2 de neisseria meningitidis
CU22559A1 (es) * 1996-01-17 1999-05-03 Ct Ingenieria Genetica Biotech Sistema de expresión de antígenos heterologos en e. coli como proteínas de fusión
DE19630390A1 (de) 1996-07-26 1998-01-29 Chiron Behring Gmbh & Co Proteine, insbesondere Membranproteine von Helicobacter pylori, ihre Herstellung und Verwendung
ATE292980T1 (de) 1996-10-11 2005-04-15 Univ California Immunostimulierende oligonucleotidekonjugate
WO1998017805A2 (en) 1996-10-24 1998-04-30 THE GOVERNMENT OF THE UNITED STATES OF AMERICA, represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, c/o Centers for Disease Control and Prevention, Technology Transfer Office Invasion associated genes from neisseria meningitidis serogroup b
AU738513B2 (en) 1997-02-28 2001-09-20 University Of Iowa Research Foundation, The Use of nucleic acids containing unmethylated CpG dinucleotide in the treatment of LPS-associated disorders
WO1998040100A1 (en) 1997-03-10 1998-09-17 Ottawa Civic Loeb Research Institute USE OF NUCLEIC ACIDS CONTAINING UNMETHYLATED CpG DINUCLEOTIDE AS AN ADJUVANT
US6299881B1 (en) 1997-03-24 2001-10-09 Henry M. Jackson Foundation For The Advancement Of Military Medicine Uronium salts for activating hydroxyls, carboxyls, and polysaccharides, and conjugate vaccines, immunogens, and other useful immunological reagents produced using uronium salts
EP1003531B1 (en) 1997-05-20 2007-08-22 Ottawa Health Research Institute Processes for preparing nucleic acid constructs
CA2293489C (en) 1997-06-06 2009-09-29 The Regents Of The University Of California Inhibitors of dna immunostimulatory sequence activity
GB9712347D0 (en) 1997-06-14 1997-08-13 Smithkline Beecham Biolog Vaccine
GB9713156D0 (en) 1997-06-20 1997-08-27 Microbiological Res Authority Vaccines
DE69815692T2 (de) 1997-09-05 2004-04-29 Glaxosmithkline Biologicals S.A. Öl in wasser emulsionen mit saponinen
US6914131B1 (en) 1998-10-09 2005-07-05 Chiron S.R.L. Neisserial antigens
EP1900818A3 (en) * 1997-11-06 2008-06-11 Novartis Vaccines and Diagnostics S.r.l. Neisserial antigens
DE69836977T2 (de) 1997-11-21 2007-10-18 Serono Genetics Institute S.A. Chlamydia pneumoniae genomische sequenzen und polypeptiden, fragmenten und anwendungen davon für nachweis, prevention und heilung
CN1280619A (zh) 1997-11-28 2001-01-17 根瑟特公司 沙眼衣原体的基因组序列和多肽,其片段以及其用途,特别是用于诊断、预防和治疗感染
GB9726398D0 (en) 1997-12-12 1998-02-11 Isis Innovation Polypeptide and coding sequences
SG152917A1 (en) 1998-01-14 2009-06-29 Chiron Srl Neisseria meningitidis antigens
ATE375393T1 (de) * 1998-01-30 2007-10-15 Asubio Pharma Co Ltd Verfahren zur herstellung eines peptids mittels eines hilfspeptids
US6303114B1 (en) 1998-03-05 2001-10-16 The Medical College Of Ohio IL-12 enhancement of immune responses to T-independent antigens
GB9807721D0 (en) 1998-04-08 1998-06-10 Chiron Spa Antigen
AU746163B2 (en) 1998-04-09 2002-04-18 Smithkline Beecham Biologicals (Sa) Adjuvant compositions
US20070026021A1 (en) 1998-05-01 2007-02-01 Chiron S.R.I. Neisseria meningitidis antigens and compositions
EP2261350A3 (en) 1998-05-01 2012-01-04 Novartis Vaccines and Diagnostics, Inc. Neisseria meningitidis antigens and compositions
US6248329B1 (en) * 1998-06-01 2001-06-19 Ramaswamy Chandrashekar Parasitic helminth cuticlin nucleic acid molecules and uses thereof
GB9817052D0 (en) 1998-08-05 1998-09-30 Smithkline Beecham Biolog Vaccine
MXPA01003557A (es) 1998-10-09 2004-04-05 Chiron Corp Secuencias genomicas de neisseria y metodos para su uso.
CA2773698C (en) 1998-10-16 2015-05-19 Glaxosmithkline Biologicals S.A. Adjuvant systems comprising an immunostimulant adsorbed to a metallic salt particle and vaccines thereof
DK1535928T3 (da) 1998-10-22 2008-10-20 Univ Montana Vaccinesammensætninger indeholdende Omp85-proteiner af Neisseria gonorrhoeae og Neisseria meningitidis
JP2002529069A (ja) 1998-11-12 2002-09-10 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア クラミジア・ニューモニエのゲノム配列
GB9828000D0 (en) 1998-12-18 1999-02-10 Chiron Spa Antigens
MY125202A (en) 1999-03-19 2006-07-31 Smithkline Beecham Biologicals S A Vaccine
FR2791895B1 (fr) 1999-03-23 2001-06-15 Pasteur Merieux Serums Vacc Utilisation de trehalose pour stabiliser un vaccin liquide
WO2000061761A2 (en) 1999-04-09 2000-10-19 Techlab, Inc. Recombinant clostridium toxin a protein carrier for polysaccharide conjugate vaccines
EP1187629B1 (en) 1999-04-19 2004-09-22 GlaxoSmithKline Biologicals S.A. Adjuvant composition comprising saponin and an immunostimulatory oligonucleotide
EP1185691B1 (en) 1999-04-30 2009-04-29 Novartis Vaccines and Diagnostics, Inc. Neisseria genomic sequences and methods of their use
US7368261B1 (en) 1999-04-30 2008-05-06 Novartis Vaccines And Diagnostics Srl Conserved Neisserial antigens
EP2258851A1 (en) 1999-05-19 2010-12-08 Novartis Vaccines and Diagnostics S.r.l. Combination neisserial compositions
GB9911683D0 (en) 1999-05-19 1999-07-21 Chiron Spa Antigenic peptides
GB9916529D0 (en) 1999-07-14 1999-09-15 Chiron Spa Antigenic peptides
HK1046861A1 (zh) 1999-09-24 2003-01-30 Smithkline Beecham Biologicals S.A. 包括聚氧乙烯烷基酯或者醚以及至少一種非離子表面活性劑的佐劑
IL148672A0 (en) 1999-09-24 2002-09-12 Smithkline Beecham Biolog Use of combination of polyxyethylene sorbitan ester and octoxynol as adjuvant and its use in vaccines
EP1801219B1 (en) 1999-10-29 2015-10-14 GlaxoSmithKline Biologicals S.A. Neisserial antigenic peptides
ATE476988T1 (de) 2000-01-17 2010-08-15 Novartis Vaccines & Diagnostic Membranvesikel (omv) impfstoff, der n. meningitidis serogruppe b membranproteine enthält
WO2001055182A1 (en) 2000-01-25 2001-08-02 The University Of Queensland PROTEINS COMPRISING CONSERVED REGIONS OF NEISSERIA MENINGITIDIS SURFACE ANTIGEN NhhA
PT1790660E (pt) * 2000-02-28 2012-09-17 Novartis Vaccines & Diagnostic Expressão heteróloga de proteínas de neisseria
US20040167058A1 (en) * 2000-06-29 2004-08-26 Colgate-Palmolive Company Multi-phase clear fabric softening composition
EP1297005B1 (en) 2000-07-03 2009-08-26 Novartis Vaccines and Diagnostics S.r.l. Immunisation against chlamydia pneumoniae
ES2330083T3 (es) 2000-10-27 2009-12-04 Novartis Vaccines And Diagnostics S.R.L. Acidos nucleicos y proteinas de estreptococos de los grupos a y b.
GB0108024D0 (en) 2001-03-30 2001-05-23 Chiron Spa Bacterial toxins
GB0118249D0 (en) 2001-07-26 2001-09-19 Chiron Spa Histidine vaccines
EP1409013B1 (en) 2001-07-26 2009-11-18 Novartis Vaccines and Diagnostics S.r.l. Vaccines comprising aluminium adjuvants and histidine
GB0121591D0 (en) 2001-09-06 2001-10-24 Chiron Spa Hybrid and tandem expression of neisserial proteins
BR0211494A (pt) 2001-07-27 2004-08-17 Chiron Srl Adesinas de meningococo nada, app e orf 40
MX339524B (es) 2001-10-11 2016-05-30 Wyeth Corp Composiciones inmunogenicas novedosas para la prevencion y tratamiento de enfermedad meningococica.
NZ587398A (en) 2002-08-02 2012-03-30 Glaxosmithkline Biolog Sa Neisserial bleb preparations and vaccines comprising them
US7785608B2 (en) 2002-08-30 2010-08-31 Wyeth Holdings Corporation Immunogenic compositions for the prevention and treatment of meningococcal disease
HUE031886T2 (en) 2002-10-11 2017-08-28 Glaxosmithkline Biologicals Sa Polypeptide vaccines for extensive protection against hypervirulent meningococcal lines
GB0227346D0 (en) 2002-11-22 2002-12-31 Chiron Spa 741
EP1590459A2 (en) 2003-01-15 2005-11-02 Wyeth Holdings Corporation Methods for increasing neisseria protein expression and compositions thereof
PT2191844E (pt) 2003-01-30 2014-06-04 Novartis Ag Vacinas injetáveis contra múltiplos serogrupos meningocócicos
MXPA05011110A (es) 2003-04-16 2006-01-24 Wyeth Corp Composiciones inmunogenicas novedosas para la prevencion y tratamiento de un padecimiento originado por meningococos.
RU2378010C2 (ru) 2003-10-02 2010-01-10 Новартис Вэксинес Энд Дайэгностикс С.Р.Л. Жидкие вакцины для множественных серогрупп менингококков
GB0409748D0 (en) 2004-04-30 2004-06-09 Chiron Srl Lactoferrin cleavage
GB0419408D0 (en) 2004-09-01 2004-10-06 Chiron Srl 741 chimeric polypeptides
AR051836A1 (es) 2004-11-30 2007-02-14 Centocor Inc Antagonistas de receptor 3 simil toll metodos y usos
CA2590974C (en) 2005-01-27 2017-10-03 Children's Hospital & Research Center At Oakland Gna1870-based vesicle vaccines for broad spectrum protection against diseases caused by neisseria meningitidis
GB0524066D0 (en) 2005-11-25 2006-01-04 Chiron Srl 741 ii
TW200806315A (en) 2006-04-26 2008-02-01 Wyeth Corp Novel formulations which stabilize and inhibit precipitation of immunogenic compositions
AR064642A1 (es) 2006-12-22 2009-04-15 Wyeth Corp Polinucleotido vector que lo comprende celula recombinante que comprende el vector polipeptido , anticuerpo , composicion que comprende el polinucleotido , vector , celula recombinante polipeptido o anticuerpo , uso de la composicion y metodo para preparar la composicion misma y preparar una composi
WO2008125985A2 (en) 2007-04-11 2008-10-23 Novartis Ag Blocking interaction between pathogen factors and factor h to inhibit hemorrhagic syndromes
NZ581367A (en) 2007-06-04 2012-05-25 Novartis Ag Formulation of meningitis vaccines containing haemophilus influenzae and neisseria meningitidis
NZ587382A (en) 2008-02-21 2012-01-12 Novartis Ag Meningococcal fhbp polypeptides
US9511131B2 (en) 2008-03-10 2016-12-06 Children's Hospital & Research Center Oakland Chimeric factor H binding proteins (fHBP) containing a heterologous B domain and methods of use
IT1394288B1 (it) 2008-09-12 2012-06-06 Novartis Vaccines & Diagnostic Immunogeni di proteine che legano il fattore h.
GB0819633D0 (en) 2008-10-25 2008-12-03 Isis Innovation Composition
ES2797504T3 (es) 2009-03-24 2020-12-02 Glaxosmithkline Biologicals Sa Proteína de enlace del factor H meningocócico utilizada como adyuvante
BR112013005626B1 (pt) 2010-09-10 2022-07-26 Glaxosmithkline Biologicals Sa Meningococo, processo para a preparação de uma cepa meningocócica, vesículas de membrana externa, composição farmacêutica imunogênica, e, uso de uma composição

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